MEPCE

Summary

MEPCE (methylphosphate capping enzyme, HGNC:20247) is a protein-coding gene on chromosome 7q22.1, encoding 7SK snRNA methylphosphate capping enzyme (Q7L2J0). S-adenosyl-L-methionine-dependent methyltransferase that adds a methylphosphate cap at the 5’-end of 7SK snRNA (7SK RNA), leading to stabilize it. It is a common-essential gene (DepMap: required in 99.6% of cancer cell lines).

Enables 7SK snRNA binding activity and RNA 5’-gamma-phosphate methyltransferase activity. Involved in RNA modification; positive regulation of protein localization to Cajal body; and positive regulation of snRNA transcription by RNA polymerase II. Located in nucleus. Part of 7SK snRNP.

Source: NCBI Gene 56257 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 86 total
• Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_019606

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20247
Approved symbol	MEPCE
Name	methylphosphate capping enzyme
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20257
Ensembl gene	ENSG00000146834
Ensembl biotype	protein_coding
OMIM	611478
Entrez	56257

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000310512, ENST00000414441, ENST00000479201, ENST00000497759, ENST00000695111, ENST00000695112, ENST00000695113, ENST00000715739

RefSeq mRNA: 5 — MANE Select: NM_019606 NM_001194990, NM_001194991, NM_001194992, NM_001363486, NM_019606

CCDS: CCDS55136, CCDS5693

Canonical transcript exons

ENST00000310512 — 4 exons

Exon	Start	End
ENSE00000977653	100432919	100433137
ENSE00000977654	100433263	100433389
ENSE00001910157	100433502	100434118
ENSE00004027764	100429831	100431689

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 96.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.2410 / max 1547.4553, expressed in 1821 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79975	21.8673	1803
79978	13.0062	1771
79977	0.7446	425
79979	0.7244	468
79976	0.6409	349
79980	0.1682	60
79982	0.0895	21

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	96.66	gold quality
right testis	UBERON:0004534	96.44	gold quality
testis	UBERON:0000473	95.03	gold quality
adult organism	UBERON:0007023	94.05	gold quality
oocyte	CL:0000023	93.93	gold quality
spleen	UBERON:0002106	93.88	gold quality
nipple	UBERON:0002030	93.28	gold quality
granulocyte	CL:0000094	93.21	gold quality
right adrenal gland	UBERON:0001233	92.87	gold quality
right adrenal gland cortex	UBERON:0035827	92.83	gold quality
adrenal cortex	UBERON:0001235	92.59	gold quality
left adrenal gland cortex	UBERON:0035825	92.49	gold quality
left adrenal gland	UBERON:0001234	92.45	gold quality
right lobe of thyroid gland	UBERON:0001119	92.37	gold quality
mucosa of stomach	UBERON:0001199	92.00	gold quality
monocyte	CL:0000576	91.92	gold quality
adrenal gland	UBERON:0002369	91.92	gold quality
leukocyte	CL:0000738	91.89	gold quality
olfactory bulb	UBERON:0002264	91.89	silver quality
ventricular zone	UBERON:0003053	91.89	gold quality
mononuclear cell	CL:0000842	91.86	gold quality
left lobe of thyroid gland	UBERON:0001120	91.85	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.68	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.65	gold quality
right ovary	UBERON:0002118	91.63	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.56	gold quality
secondary oocyte	CL:0000655	91.54	gold quality
hair follicle	UBERON:0002073	91.48	gold quality
stromal cell of endometrium	CL:0002255	91.47	gold quality
thymus	UBERON:0002370	91.44	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting MEPCE, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-181A-2-3P	98.91	67.60	1168

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• Capping enzyme can play a direct role in transcription by modulating displacement of nascent RNA during transcription. (PMID:17978174)
• Data indicate the binding of RNA-binding protein HEXIM with 7SKsnRNP complex comprising the non-coding RNA 7SK and proteins MePCE and LARP7. (PMID:25863285)
• The 7SK small nuclear RNP (snRNP), composed of the 7SK small nuclear RNA (snRNA), MePCE, and Larp7, also functions as a canonical transcription factor that, in collaboration with the little elongation complex (LEC) comprising ELL, Ice1, Ice2, and ZC3H8, promotes transcription of RNAPII-specific spliceosomal snRNA and small nucleolar RNA (snoRNA) genes. (PMID:28254838)
• our results suggest that crosstalk between the histone-binding and RNA methylation activities of MePCE regulates P-TEFb activation on chromatin in a 7SK- and Brd4-independent manner. (PMID:29425494)
• HEXIM1 Diffusion in the Nucleus Is Regulated by Its Interactions with Both 7SK and P-TEFb. (PMID:31590891)
• Long noncoding RNA ST8SIA6AS1 promotes the migration and invasion of hypoxiatreated hepatocellular carcinoma cells through the miR338/MEPCE axis. (PMID:33416148)
• Excessive transcription-replication conflicts are a vulnerability of BRCA1-mutant cancers. (PMID:36928661)
• LARP3, LARP7, and MePCE are involved in the early stage of human telomerase RNA biogenesis. (PMID:39009594)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	mepceb	ENSDARG00000035771
danio_rerio	mepcea	ENSDARG00000059461
mus_musculus	Mepce	ENSMUSG00000029726
rattus_norvegicus	Mepce	ENSRNOG00000001387
drosophila_melanogaster	CG1239	FBGN0037368
drosophila_melanogaster	bin3	FBGN0263144
caenorhabditis_elegans		WBGENE00012469

Paralogs (1): BCDIN3D (ENSG00000186666)

Protein

Protein identifiers

7SK snRNA methylphosphate capping enzyme — Q7L2J0 (reviewed: Q7L2J0)

Alternative names: Bicoid-interacting protein 3 homolog

All UniProt accessions (2): Q7L2J0, A0A8Q3WKJ6

UniProt curated annotations — full annotation on UniProt →

Function. S-adenosyl-L-methionine-dependent methyltransferase that adds a methylphosphate cap at the 5’-end of 7SK snRNA (7SK RNA), leading to stabilize it. Also has a non-enzymatic function as part of the 7SK RNP complex: the 7SK RNP complex sequesters the positive transcription elongation factor b (P-TEFb) in a large inactive 7SK RNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation. The 7SK RNP complex also promotes snRNA gene transcription by RNA polymerase II via interaction with the little elongation complex (LEC). In the 7SK RNP complex, MEPCE is required to stabilize 7SK RNA and facilitate the assembly of 7SK RNP complex. MEPCE has a non-enzymatic function in the 7SK RNP complex; interaction with LARP7 within the 7SK RNP complex occluding its catalytic center. Also required for stability of U6 snRNAs.

Subunit / interactions. Core component of the 7SK RNP complex, at least composed of 7SK RNA, LARP7, MEPCE, HEXIM1 (or HEXIM2) and P-TEFb (composed of CDK9 and CCNT1/cyclin-T1). Interacts with METTL16. Interacts with RBM7; upon genotoxic stress this interaction is enhanced, triggering the release of inactive P-TEFb complex from the core, yielding to P-TEFb complex activation.

Subcellular location. Nucleus.

Tissue specificity. Expressed in chronic myeloid leukemia cells, adrenal gland, brain, cerebellum, kidney, lung, mammary gland and testis. Weakly or not expressed in other tissues.

Post-translational modifications. Dephosphorylated at Ser-152 by the PNUTS-PP1 complex, promoting RNA polymerase II transcription pause-release.

Similarity. Belongs to the methyltransferase superfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7L2J0-1	1	yes
Q7L2J0-2	2

RefSeq proteins (5): NP_001181919, NP_001181920, NP_001181921, NP_001350415, NP_062552* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010675	Bin3_C	Domain
IPR024160	BIN3_SAM-bd_dom	Domain
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR039772	Bin3-like	Family

Pfam: PF06859

Catalyzed reactions (Rhea), 1 shown:

• a 5’-end triphospho-guanosine-ribonucleotide-snRNA + S-adenosyl-L-methionine = a 5’-end methyltriphosphate-guanosine-ribonucleotide-snRNA + S-adenosyl-L-homocysteine (RHEA:58780)

UniProt features (65 total): modified residue 17, helix 14, strand 7, binding site 6, mutagenesis site 5, compositionally biased region 5, region of interest 3, turn 3, chain 1, domain 1, cross-link 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6DCB	X-RAY DIFFRACTION	2
6DCC	X-RAY DIFFRACTION	2.1
5UNA	X-RAY DIFFRACTION	2.55
7SLQ	ELECTRON MICROSCOPY	3.7
7SLP	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L2J0-F1	64.25	0.32

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (6): 422; 433; 451–453; 474–475; 559–560; 581

Post-translational modifications (18): 1, 57, 60, 69, 101, 117, 152, 175, 179, 213, 216, 217, 254, 291, 330, 344, 390, 643

Mutagenesis-validated functional residues (5):

Position	Phenotype
152	promotes rna polymerase ii transcription pause-release.
421	nearly abolished methyltransferase activity.
447–449	abolished methyltransferase activity and reduced interaction with larp7, without affecting interaction with p-tefb.
585	decreased methyltransferase activity.
674	strongly reduced methyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 237 (showing top): RNGTGGGC_UNKNOWN, TGCGCANK_UNKNOWN, E2F4DP1_01, GCM_GSPT1, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GGGTGGRR_PAX4_03, GOBP_RNA_METHYLATION, GOBP_POSITIVE_REGULATION_OF_G1_S_TRANSITION_OF_MITOTIC_CELL_CYCLE, GCM_BCL2L1

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), RNA methylation (GO:0001510), snRNA metabolic process (GO:0016073), snRNA modification (GO:0040031), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), positive regulation of protein localization to Cajal body (GO:1904871), positive regulation of snRNA transcription by RNA polymerase II (GO:1905382), methylation (GO:0032259)

GO Molecular Function (10): RNA binding (GO:0003723), O-methyltransferase activity (GO:0008171), RNA methyltransferase activity (GO:0008173), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), snRNA binding (GO:0017069), 7SK snRNA binding (GO:0097322), RNA 5’-gamma-phosphate methyltransferase activity (GO:1990276), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (3): nucleus (GO:0005634), 7SK snRNP (GO:0120259), ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
methyltransferase activity	3
RNA modification	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
macromolecule methylation	1
RNA metabolic process	1
snRNA processing	1
G1/S transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
positive regulation of protein localization to nucleus	1
protein localization to Cajal body	1
regulation of protein localization to Cajal body	1
snRNA transcription by RNA polymerase II	1
positive regulation of transcription by RNA polymerase II	1
regulation of snRNA transcription by RNA polymerase II	1
metabolic process	1
nucleic acid binding	1
catalytic activity, acting on RNA	1
RNA binding	1
snRNA binding	1
O-methyltransferase activity	1
RNA methyltransferase activity	1
S-adenosylmethionine-dependent methyltransferase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
small nuclear ribonucleoprotein complex	1
protein-containing complex	1

Protein interactions and networks

STRING

2556 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEPCE	HEXIM1	O94992	999
MEPCE	LARP7	Q4G0J3	999
MEPCE	HEXIM2	Q96MH2	997
MEPCE	CDK9	P50750	988
MEPCE	CCNT1	O60563	962
MEPCE	BIN3	Q9NQY0	921
MEPCE	SART3	Q15020	875
MEPCE	CCNT2	O60583	866
MEPCE	AFF1	P51825	797
MEPCE	AFF4	Q9UHB7	778
MEPCE	RBM8A	Q9Y5S9	751
MEPCE	BRD4	O60885	744
MEPCE	MLLT1	Q03111	659
MEPCE	MLLT3	P42568	640
MEPCE	PPM1G	O15355	634

IntAct

183 interactions, top by confidence:

A	B	Type	Score
CDK9	CCNT1	psi-mi:“MI:0914”(association)	0.980
LSM3	LSM1	psi-mi:“MI:0914”(association)	0.950
HEXIM1	CCNT1	psi-mi:“MI:0914”(association)	0.930
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
LARP7	CCNT1	psi-mi:“MI:0914”(association)	0.850
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
HEXIM2	AHCYL1	psi-mi:“MI:0914”(association)	0.740
SART3	PRPF4	psi-mi:“MI:0914”(association)	0.730
CDK9	AIP	psi-mi:“MI:0914”(association)	0.730
PRPF3	PRPF4	psi-mi:“MI:0914”(association)	0.730

BioGRID (1098): MEPCE (Affinity Capture-MS), CHMP3 (Affinity Capture-MS), HNRNPA1 (Affinity Capture-MS), MEPCE (Affinity Capture-MS), MEPCE (Affinity Capture-MS), MEPCE (Affinity Capture-MS), MEPCE (Affinity Capture-MS), MEPCE (Affinity Capture-MS), MEPCE (Affinity Capture-MS), MEPCE (Co-fractionation), MEPCE (Affinity Capture-MS), MEPCE (Affinity Capture-MS), MEPCE (Affinity Capture-MS), MEPCE (Affinity Capture-MS), MEPCE (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IZ84, A3KQ55, A5PKL1, A6NIR3, A6QP06, A7J1T0, A7J1T2, D3ZU96, O60563, O70445, P0C2N5, P55197, P61406, Q12830, Q14693, Q2PFD7, Q3U8K7, Q4FZB7, Q4KMM3, Q5HZN1, Q5RAK6, Q5RJX8, Q5SPL2, Q5U3H2, Q5VUJ5, Q6A0A2, Q6IRB8, Q6NN85, Q6T8E9, Q7L2J0, Q7ZXG4, Q801E2, Q86US8, Q8BRB7, Q8HXN7, Q8IYH5, Q8K298, Q8K3A9, Q8WYB5, Q90YL3

Diamond homologs: A3KQ55, D4ABH7, Q29S19, Q5RFI3, Q6NPC9, Q7K480, Q7L2J0, Q7T0L7, Q7Z5W3, Q8K3A9, Q91YP1, Q9U2R0, Q9VNH1, Q9VZD2, A8E7D2, A0K4C9, A5IN97, A6LJG3, A9AI41, B1JVC0, B1L841, B4E5V2, B5YDR3, B7IFP7, B8E1A7, Q1BZC1, Q39JS9, Q9X0G8, Q9Y7L2, A0KNJ1, A1AGF9, A1JRL5, A4WF74, A6TES6, A7FDQ3, A7ZSF3, A8A570, A8AQF7, A8GK75, A9MNA2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
JMJD6	“down-regulates activity”	MEPCE	cleavage
MEPCE	“down-regulates activity”	P-TEFb	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 167 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA decay by 5’ to 3’ exoribonuclease	7	48.0×	3e-09
Metabolism of non-coding RNA	7	40.0×	1e-08
RNA Polymerase II Transcription Termination	12	23.7×	7e-12
SARS-CoV-2 modulates host translation machinery	11	22.2×	2e-10
mRNA Splicing	21	20.8×	4e-20
Transport of Mature Transcript to Cytoplasm	6	20.6×	1e-05
Processing of Capped Intron-Containing Pre-mRNA	23	17.0×	4e-20
mRNA Splicing - Minor Pathway	8	16.1×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	11	42.3×	3e-13
RNA splicing, via transesterification reactions	6	24.8×	1e-05
U2-type prespliceosome assembly	5	20.7×	3e-04
mRNA splicing, via spliceosome	24	14.6×	2e-18
regulation of alternative mRNA splicing, via spliceosome	9	14.6×	2e-06
cytoplasmic translation	11	13.5×	1e-07
RNA splicing	19	11.1×	2e-12
ribosomal small subunit biogenesis	6	9.1×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

86 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

599 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100432917:A:AG	acceptor_gain	1.0000
7:100432917:AG:A	acceptor_gain	1.0000
7:100432918:G:GG	acceptor_gain	1.0000
7:100432918:GG:G	acceptor_gain	1.0000
7:100432918:GGGT:G	acceptor_gain	1.0000
7:100432918:GGGTA:G	acceptor_gain	1.0000
7:100433133:TTACA:T	donor_gain	1.0000
7:100433134:TACA:T	donor_gain	1.0000
7:100433138:G:GG	donor_gain	1.0000
7:100433143:T:G	donor_gain	1.0000
7:100433259:TTAG:T	acceptor_loss	1.0000
7:100433261:A:AG	acceptor_gain	1.0000
7:100433261:AG:A	acceptor_gain	1.0000
7:100433262:G:A	acceptor_gain	1.0000
7:100433262:G:GA	acceptor_gain	1.0000
7:100433262:GGA:G	acceptor_gain	1.0000
7:100433262:GGAA:G	acceptor_gain	1.0000
7:100433262:GGAAA:G	acceptor_gain	1.0000
7:100433387:AAGG:A	donor_loss	1.0000
7:100433388:AGGTA:A	donor_loss	1.0000
7:100433389:GGT:G	donor_loss	1.0000
7:100433390:G:C	donor_loss	1.0000
7:100433390:G:GG	donor_gain	1.0000
7:100433391:T:A	donor_loss	1.0000
7:100428586:T:A	donor_gain	0.9900
7:100429799:T:G	donor_gain	0.9900
7:100431687:ACG:A	donor_loss	0.9900
7:100431688:CGGT:C	donor_loss	0.9900
7:100431690:G:C	donor_loss	0.9900
7:100431690:G:GG	donor_gain	0.9900

AlphaMissense

4397 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100430571:T:C	F185L	1.000
7:100430572:T:C	F185S	1.000
7:100430573:C:A	F185L	1.000
7:100430573:C:G	F185L	1.000
7:100430580:G:A	G188R	1.000
7:100430580:G:C	G188R	1.000
7:100430581:G:A	G188E	1.000
7:100430583:G:C	G189R	1.000
7:100430584:G:T	G189V	1.000
7:100430596:A:G	D193G	1.000
7:100430596:A:T	D193V	1.000
7:100430602:T:A	L195Q	1.000
7:100430602:T:C	L195P	1.000
7:100430608:T:A	L197Q	1.000
7:100430608:T:C	L197P	1.000
7:100430704:T:C	I229T	1.000
7:100430734:T:A	L239H	1.000
7:100430734:T:C	L239P	1.000
7:100431264:G:T	G416W	1.000
7:100431265:G:A	G416E	1.000
7:100431265:G:T	G416V	1.000
7:100431279:T:C	Y421H	1.000
7:100431286:G:A	G423E	1.000
7:100431339:T:A	W441R	1.000
7:100431339:T:C	W441R	1.000
7:100431343:T:C	F442S	1.000
7:100431358:T:A	V447D	1.000
7:100431361:T:C	L448P	1.000
7:100431369:G:C	G451R	1.000
7:100431373:G:A	C452Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000000630 (7:100432796 G>A), RS1000333534 (7:100428392 C>T), RS1000499934 (7:100432794 C>T), RS1000645204 (7:100427491 G>A,C,T), RS1000676116 (7:100427923 C>G), RS1001953498 (7:100430154 G>A), RS1002010888 (7:100430048 G>A,C), RS1002139125 (7:100433725 C>T), RS1002542116 (7:100434451 G>A), RS1002682594 (7:100429661 C>A,G,T), RS1002962185 (7:100434304 G>A), RS1003059858 (7:100429480 A>G), RS1003653921 (7:100430444 T>G), RS1004027652 (7:100430272 A>T), RS1004564928 (7:100430194 G>C,T)

Disease associations

OMIM: gene MIM:611478 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010702_48	Subcortical volume (MOSTest)	6.000000e-10
GCST010703_289	Brain morphology (MOSTest)	6.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	8
trichostatin A	decreases expression	2
Vorinostat	decreases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
ferrous chloride	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	increases phosphorylation	1
HC toxin	decreases expression	1
apicidin	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
suberoyl bis-hydroxamic acid	decreases expression	1
Leflunomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Bleomycin	increases expression	1
Caffeine	increases phosphorylation	1
Coumestrol	increases expression, affects cotreatment	1
Deoxyglucose	increases expression	1

Clinical trials (associated diseases)

202 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice